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Fecal microbiota transplantion improves cognition in old 5XFAD Alzheimer's mice

Shalini Elangovan (1), Thomas Borody (2) and R. M. Damian Holsinger (1, 3)

  1. Laboratory of Molecular Neuroscience and Dementia, Brain and Mind Centre, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia

  2. Centre for Digestive Diseases, Level 1, 229 Great North Road, Five Dock, New South Wales, Australia

  3. Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

The intestinal microbiome has been shown to play a significant role in health and disease. The human bowel contains a complex population of bacteria and the chemicals they produce have both positive and negative impacts on health. Feacal Microbiota Transplant (FMT) involves the infusion of healthy human donor faeces via endoscopic procedures and/or enema treatments into the bowel of the recipient, aiding the repair of the microbiome. Replenishing the gut microbiome with healthy donor fecal microbiota transplants has been established as a treatment for diseases such as Chron’s, ulcerative colitis and Clostridium difficile infection (CDI). The involvement of the intestinal microbial environment in neurodegenerative diseases such as Alzheimer’s and Parkinson’s has recently been demonstrated, prompting investigation into the restoration of gut microbiota in an attempt to reduce cognitive and behavioral deficits associated with these diseases. Here we demonstrate the efficacy of FMT in Alzheimer’s disease whereby treatment resulted in significantly improved cognition in old (30-32 weeks) transgenic 5xFAD Alzheimer’s mice following fecal slurry transfer from healthy wild-type littermates (Old Tg-FO). Administration of fecal slurry for 7 days followed by a 3-week incubation period resulted in significant improvements spatial learning and memory as well as enhanced recognition memory in treated mice compared to age-matched, Old Tg-Control mice receiving saline. We demonstrate for the first time, the benefits of FMT in improving cognition in an aged, robust mouse model of Alzheimer’s.